{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T16:41:23Z","timestamp":1772210483440,"version":"3.50.1"},"reference-count":82,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T00:00:00Z","timestamp":1705708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["FWUR-2024-0040"],"award-info":[{"award-number":["FWUR-2024-0040"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2021-1355"],"award-info":[{"award-number":["075-15-2021-1355"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Computation"],"abstract":"<jats:p>Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) virus syndrome caused the recent outbreak of COVID-19 disease, the most significant challenge to public health for decades. Despite the successful development of vaccines and promising therapies, the development of novel drugs is still in the interests of scientific society. SARS-CoV-2 main protease Mpro is one of the key proteins for the lifecycle of the virus and is considered an intriguing target. We used a structure-based drug design approach as a part of the search of new inhibitors for SARS-CoV-2 Mpro and hence new potential drugs for treating COVID-19. Four structures of potential inhibitors of (4S)-2-(2-(1H-imidazol-5-yl)ethyl)-4-amino-2-(1,3-dihydroxypropyl)-3-hydroxy-5-(1H-imidazol-5-yl)pentanal (L1), (2R,4S)-2-((1H-imidazol-4-yl)methyl)-4-chloro-8-hydroxy-7-(hydroxymethyl)octanoic acid (L2), 1,9-dihydroxy-6-(hydroxymethyl)-6-(((1S)-1,7,7-trimethylbicyclo [2.2.1]heptan-2-yl)amino)nonan-4-one (L3), and 2,4,6-tris((4H-1,2,4-triazol-3-yl)amino)benzonitrile (L4) were modeled. Three-dimensional structures of ligand\u2013protein complexes were modeled and their potential binding efficiency proved. Docking and molecular dynamic simulations were performed for these compounds. Detailed trajectory analysis of the ligands\u2019 binding conformation was carried out. Binding free energies were estimated by the MM\/PBSA approach. Results suggest a high potential efficiency of the studied inhibitors.<\/jats:p>","DOI":"10.3390\/computation12010018","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T03:50:22Z","timestamp":1705895422000},"page":"18","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Computer Aided Structure-Based Drug Design of Novel SARS-CoV-2 Main Protease Inhibitors: Molecular Docking and Molecular Dynamics Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8988-5703","authenticated-orcid":false,"given":"Dmitry S.","family":"Kolybalov","sequence":"first","affiliation":[{"name":"SRF \u201cSKIF\u201d, 630559 Koltsovo, Russia"},{"name":"Scientific Educational Center \u201cInstitute of Chemical Technology\u201d, Novosibirsk State University, 630090 Novosibirsk, Russia"}]},{"given":"Evgenii D.","family":"Kadtsyn","sequence":"additional","affiliation":[{"name":"SRF \u201cSKIF\u201d, 630559 Koltsovo, Russia"},{"name":"Voevodsky Institute of Chemical Kinetics and Combustion, 630090 Novosibirsk, Russia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4812-3037","authenticated-orcid":false,"given":"Sergey G.","family":"Arkhipov","sequence":"additional","affiliation":[{"name":"SRF \u201cSKIF\u201d, 630559 Koltsovo, Russia"},{"name":"Scientific Educational Center \u201cInstitute of Chemical Technology\u201d, Novosibirsk State University, 630090 Novosibirsk, Russia"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A Pneumonia Outbreak Associated with a New Coronavirus of Probable Bat Origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","article-title":"A New Coronavirus Associated with Human Respiratory Disease in China","volume":"579","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ijid.2020.01.009","article-title":"The Continuing 2019-NCoV Epidemic Threat of Novel Coronaviruses to Global Health\u2014The Latest 2019 Novel Coronavirus Outbreak in Wuhan, China","volume":"91","author":"Hui","year":"2020","journal-title":"Int. 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